Paraproteinemia - An Insight Into Paraproteinemia

What Is Paraprotein?

Proteins are found in the tissues of all living organisms. Antibodies are a type of proteins that are produced by the body’s immune system in response to any foreign substance. For example, plasma cells (a type of white blood cell) produced in the body’s bone marrow produce antibodies in response to microbial infections. Sometimes, the plasma cells also produce abnormal proteins. These proteins are known as paraproteins. These are also known as monoclonal immunoglobulin or M - proteins. The presence of these proteins in blood or urine indicates a diseased condition.

What Is Paraproteinemia?

The presence of the paraprotein in the body is known as paraproteinemia. The most common paraproteinemia condition is monoclonal gammopathy of unknown significance (MGUS). It is non-cancerous, but people with MGUS are at high risk of developing severe blood and bone marrow (myeloma and lymphoma) disorders.

What Are the Disorders Associated With Paraproteinemia?

Paraproteins are the product of B-cell clones. They can be large, small, or undiagnosed in a routine investigation. B-cell disorders are the result of circulating paraproteins in the blood. The disorders associated with paraprotein monoclonal gammopathy are of unknown significance. The disorders of paraproteinemia are as follows:

• Malignant B-cell disorder.

• Multiple myeloma; both symptomatic and asymptomatic myeloma.

• Lymphoproliferative disorders.

• Plasmacytoma.

• MGUS (Monoclonal Gammopathy of Unknown Significance) - Paraprotein is detected with no other B-cell disorder.

• Non-malignant Systemic Disease- The paraproteins detected is small. Therefore, in these disorders, neither the B-cell clone nor the monoclonal protein is clinically significant, and it cannot be categorized into MGUS due to existing systemic conditions.

  • Autoimmune diseases like rheumatoid arthritis.

  • Liver disease like hepatitis.

  • Infectious diseases like bacterial endocarditis and mycobacterium tuberculosis.

  • Cutaneous diseases like xanthoma and pyoderma gangrenosum.

How Does M-Protein Develop?

The plasma cells of the bone marrow produce antibodies that fight against infections and foreign bodies. However, in plasma cell disorders like multiple myeloma, the plasma cells grow uncontrollably and outnumber cells in the bone marrow and blood, along with the production of antibodies called paraprotein or M proteins. As a result of paraproteins, several health complications like bone problems, frequent infections, impaired kidneys, and anemia develop.

What Is the Pathogenesis of Disorders Associated With Paraprotein?

The disorders related to paraprotein develop in two ways:

• The monoclonal antibodies group together and deposit systemically in diseases like cryoglobulinemia type 1 (a form of inflammation of blood vessels) and light chain amyloidosis.

• Paraproteins exhibit antibody activity toward autogenous antigens resulting in disorders like polyneuropathy and cryoglobulinemia type 2.

What Are the Indications for Screening of M-Protein or Paraprotein?

Paraproteins are mainly found during routine investigations. However, screening is necessary if the patient presents the following symptoms:

• Fatigue and body aches.

• Bone disease

• Kidney and liver-related problems.

• Increased calcium level.

• Repeated bacterial infections.

• Neurological problems like peripheral neuropathy and carpal tunnel syndrome.

• Continuously increased erythrocyte sedimentation rate.

How Is Paraproteinemia Diagnosed?

The diagnosis of paraproteinemia includes:

• Blood Test- Complete blood count is advised to measure the amount and type of paraprotein made by the plasma cells and different blood cells. Calcium levels are also checked since myeloma can increase calcium levels.

• Urine Test- It is done as urine analysis might also detect the presence of paraproteins.

• X-Rays- X-rays are advised to check the damage caused by myeloma.

• Magnetic Resonance Imaging (MRI)- It is advised by doctors whenever necessary.

• Biopsy- A sample of bone marrow is taken to check for the presence of abnormal cells.

How Is MGUS (Monoclonal Gammopathy of Unknown Significance) Different From Myeloma?

Based on the paraprotein level in the blood, the percentage of plasma cells in the bone marrow, and the presence or absence of organs affected by myeloma, the patients are divided into three groups: MGUS, asymptomatic myeloma, and symptomatic myeloma. Asymptomatic myeloma and MGUS evolve into symptomatic myeloma. Myeloma goes unrecognized in the early stage due to its asymptomatic nature. There is no specific treatment for asymptomatic myeloma, and the patients should be educated about the disease and associated conditions to improve their life.

What Is the Treatment of MGUS (Monoclonal Gammopathy of Unknown Significance)?

Usually, treatment is not needed for MGUS since it rarely shows any symptoms. Mostly MGUS remains stable and seldom causes problems in the person. The chances of MGUS converting into lymphoma (cancer of the blood) and myeloma (cancer of bone marrow) are meager. If in case MGUS converts into cancer, they grow very slowly. Patients should take medical advice for any of the below-mentioned symptoms:

• Constant bone pain (in the back, pelvis, etc.).

• Recurrent infections.

• New lumps and swellings.

• Extreme tiredness.

• Weight loss.

The doctor conducts regular blood tests. During the first year, blood tests are performed more frequently. Blood tests are conducted less often if the blood test is normal and there are no new symptoms.

What Is the Treatment for Myeloma?

Myeloma treatment can be directed explicitly against malignant plasma cells or supportive care to prevent complications of bone marrow, kidney, and skeletal tissues occurring in myeloma. Drug of choice is Thalidomide. However, recently Lenalidomide has been used due to the side effects caused by Thalidomide. Supportive care in myeloma treatment includes:

• Pain Control- Pain is the most common symptom experienced by patients. It is treated with opioid analgesics and interventions like radiotherapy, neurosurgery, and orthopedic surgery.

• Hypercalcemia- It is mainly present in patients with symptoms. Management of hypercalcemia is done by rehydrating the body with saline and Furosemide and with medications like Bisphosphonates.

• Renal Impairment- The kidney is easily affected in myeloma due to hypercalcemia, hyperuricemia, and the use of medicines that cause kidney damage. Therefore, a biopsy is advised, after which treatment is planned for the patients.

• Anemia- Anemia is common in myeloma patients. It is managed by transfusing red blood cells and using recombinant erythropoietin.

• Infections- There is a high chance of infections in myeloma patients due to treatment and the disease itself. Using steroids and chemotherapy results in a weakened immune system and hence conditions. Managed by antibiotics.

• AL Amyloidosis- Patients with myeloma develop AL amyloidosis resulting in cardiac failure, renal failure, and neuropathy complications. Treatment is based on the symptoms that appear (symptomatic treatment).

Conclusion

Paraprotein finding is quite common in patients, with MGUS being the most common disorder. Therefore, it is essential to differentiate MGUS from asymptomatic and symptomatic myeloma and plan the treatment properly. Symptomatic myeloma is incurable however proper treatment plan prolongs life expectancy along with good life.